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Showing papers in "Rheumatology International in 2012"


Journal ArticleDOI
TL;DR: While strategies and guidelines aimed at reducing NSAID-associated complications exist, there is a need for evidence-based algorithms combining cardiovascular and gastrointestinal factors that can be used to aid treatment decisions at an individual patient level.
Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) represent a diverse class of drugs and are among the most commonly used analgesics for arthritic pain worldwide, though long-term use is associated with a spectrum of adverse effects. The introduction of cyclooxygenase-2-selective NSAIDs early in the last decade offered an alternative to traditional NSAIDs with similar efficacy and improved gastrointestinal tolerability; however, emerging concerns about cardiovascular safety resulted in the withdrawal of two agents (rofecoxib and valdecoxib) in the mid-2000s and, subsequently, in an overall reduction in NSAID use. It is now understood that all NSAIDs are associated with some varying degree of gastrointestinal and cardiovascular risk. Guidelines still recommend their use, but little is known of how patients use these agents. While strategies and guidelines aimed at reducing NSAID-associated complications exist, there is a need for evidence-based algorithms combining cardiovascular and gastrointestinal factors that can be used to aid treatment decisions at an individual patient level.

314 citations


Journal ArticleDOI
Qian Niu1, Bei Cai1, Zhuochun Huang1, Yunying Shi1, Lanlan Wang1 
TL;DR: This study indicated that development of RA is associated with peripheral Th17/Treg imbalance and characterized by a proinflammatory cytokine microenvironment, which supports continuing generation of Th17 cells.
Abstract: Proinflammatory Th17 cells and CD4(+)CD25(+) regulatory T (Treg) cells are two newly identified T lymphocyte subsets, which have opposite effects on autoimmunity and inflammation. To assess the Th17/Treg pattern and cytokine microenvironment in peripheral blood of patients with RA, we included 66 RA patients and 20 healthy volunteers. Of all these subjects, peripheral Th17 and Treg frequencies were analyzed by flow cytometry (FCM) and the plasma levels of interleukin (IL)-17, 23, 6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 were detected by ELISA. The results demonstrated that RA patients revealed an obvious increase in peripheral Th17 frequencies and levels of Th17-related cytokines (IL-17, IL-23, IL-6, TNF-α) while a significant decrease in Treg frequencies and Treg-related cytokine (TGF-β1) levels when compared with healthy people. Our study indicated that development of RA is associated with peripheral Th17/Treg imbalance and characterized by a proinflammatory cytokine microenvironment, which supports continuing generation of Th17 cells.

195 citations


Journal ArticleDOI
Wenhong Wang1, Shihe Shao1, Zhijun Jiao1, Mingquan Guo, Huaxi Xu1, Shengjun Wang1 
TL;DR: The results demonstrated that active RA patients exhibited increased peripheral Th17 cells, Th1- and Th17-related cytokines and RORγt expression while decreased Treg cells and FoxP3 expression, which indicated that Th17/Treg balance was broken in peripheral blood.
Abstract: Broken Th17/Treg balance has been reported contributing to several inflammatory autoimmune diseases. The objective of the study was to investigate whether the Th17/Treg balance was impaired in the peripheral blood of patients with rheumatoid arthritis (RA). The frequencies of Treg cells and Th17 cells and mRNA expression of transcription factor RORγt and FoxP3 in peripheral blood of RA patients (n = 37) and healthy controls (n = 30) were determined by flow cytometry and real-time PCR, respectively. Eleven serum cytokines were analyzed by using cytometeric bead array (CBA). The results demonstrated that active RA patients exhibited increased peripheral Th17 cells, Th1- and Th17-related cytokines and RORγt expression while decreased Treg cells and FoxP3 expression. In addition, Th17/Treg ratios were positively correlated with serum concentrations of Th1- and Th17-related cytokines. In conclusion, our results indicated that Th17/Treg balance was broken in peripheral blood, which may play an important role in the development of RA.

194 citations


Journal ArticleDOI
TL;DR: Some newer alternative journal metrics such as SCImago Journal Rank and the h-index are presented and examples of their application in several subject categories are analyzed and misuses of JIF are discussed.
Abstract: The highly popular journal impact factor (JIF) is an average measure of citations within 1 year after the publication of a journal as a whole within the two preceding years. It is widely used as a proxy of a journal's quality and scientiWc prestige. This article discusses misuses of JIF to assess impact of separate journal articles and the eVect of several manuscript versions on JIF. It also presents some newer alternative journal metrics such as SCImago Journal Rank and the h-index and analyses examples of their appli- cation in several subject categories.

152 citations


Journal ArticleDOI
TL;DR: An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method are presented.
Abstract: Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.

135 citations


Journal ArticleDOI
Qian Xing1, Bin Wang1, Houheng Su, Jiajia Cui, Jinghua Li 
TL;DR: The significantly elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in lupus nephritis, suggesting that Th17/Treg functional imbalance may be involved in the pathogenesis of renal damage in SLE patients.
Abstract: To investigate the variations of T-helper 17 (Th17) and regulatory T (Treg) cells in patients with lupus nephritis (LN), a total of 60 systemic lupus erythematosus patients and 28 healthy controls (HCs) were enrolled. The frequency of Th17 cells and Treg cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometric analysis. The serum concentrations of interleukin-17 (IL-17) and transforming growth factor-beta 1 (TGF-β1) were measured by enzyme-linked immunosorbent assay (ELISA). The results demonstrated in LN patients a significant decrease in the frequency of CD4+CD25high and CD4+CD25+FoxP3+ T cells and a significant increase in the frequency of Th17 cells in peripheral blood, and the ratio of Th17 to Treg cell frequency was significantly increased along with increased SLEDAI scores. LN patients had a lower percentage and expression of FoxP3 in CD4+CD25high T cells than SLE patients without nephritis. The concentration of TGF-β1 was found decreased in SLE patients compared with that from healthy controls, though no significant difference was found between LN patients and SLE patients without nephritis. The expression of IL-17 levels in LN patients exhibited a significant increase compared with patients without nephritis and healthy controls. Based on our results, the significantly elevated Th17 cells are accompanied by FoxP3+ Treg cells decrease in lupus nephritis, suggesting that Th17/Treg functional imbalance may be involved in the pathogenesis of renal damage in SLE patients.

122 citations


Journal ArticleDOI
TL;DR: This meta-analysis demonstrates that the 5-HT2A receptor 102T/C polymorphism confers susceptibility to fibromyalgia.
Abstract: The aim of this study was to explore whether the candidate gene polymorphisms contribute to fibromyalgia susceptibility. The authors conducted a meta-analysis on associations between serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) S/L allele, catechol-O-methltransferase (COMT) val158Met, and serotonin 2A (5-HT2A) receptor 102T/C polymorphisms and fibromyalgia susceptibility as determined using the following: (1) allele contrast, (2) recessive, (3) dominant models, and (4) contrast of homozygotes. We also performed a systematic review with available data of the candidate genes. A total of 21 separate comparisons were considered in this systematic review and meta-analysis. Seventeen candidate genes and over 35 different polymorphisms were identified in studies on fibromyalgia susceptibility. Meta-analysis of the 5-HTTLPR S/L allele and COMT val158Met failed to reveal any association with fibromyalgia. However, meta-analysis of the C allele, CC + CT genotype, and CC versus TT genotype of the 5-HT2A receptor 102T/C polymorphism showed significant association with fibromyalgia. The overall OR of the association between the C allele and fibromyalgia was 1.333 (95% CI = 1.053–1.688, P = 0.017). The ORs for the CC + CT genotype, and CC versus TT genotype showed the same pattern as that observed for the C allele (OR = 1.541, 95% CI = 1.032–2.303, P = 0.035; OR = 1.838, 95% CI = 1.151–2.936, P = 0.011). This meta-analysis demonstrates that the 5-HT2A receptor 102T/C polymorphism confers susceptibility to fibromyalgia. In contrast, no association was found between the 5-HTTLPR S/L allele, COMT val158Met, and susceptibility to fibromyalgia.

121 citations


Journal ArticleDOI
TL;DR: The data indicated that increased plasma HMGB1 was associated with disease activity in SLE, which was similar to TNF-alpha, and high level of plasma IFN-alpha may be related to nephritis and thrombocytopenia in S LE.
Abstract: Recent studies indicate that high-mobility group box protein 1 (HMGB1) contributes to the pathogenesis of diverse autoimmune disorders. It induces the production of interferon-alpha (IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) in vitro. In the present study, plasma HMGB1, TNF-alpha, and IFN-alpha were determined with ELISA in 37 patients with systemic lupus erythematosus (SLE) and 39 age- and sex-matched healthy controls (HC). The possible associations of these cytokines with disease activities, autoantibodies, and certain laboratory parameters were also explored. The plasma levels of HMGB1, TNF-alpha, and IFN-alpha were increased in SLE patients compared with those of HC (P < 0.05). Moreover, the levels of HMGB1 and TNF-alpha in the active SLE patients were elevated compared with those in inactive patients and HC. Additionally, plasma HMGB1 was positively correlated with peripheral neutrophils, and plasma TNF-alpha was positively correlated with anti-Sm, ESR and CRP, while plasma IFN-alpha was inversely correlated with the age and platelet level in SLE patients. Our data indicated that increased plasma HMGB1 was associated with disease activity in SLE, which was similar to TNF-alpha. High level of plasma IFN-alpha may be related to nephritis and thrombocytopenia in SLE.

108 citations


Journal ArticleDOI
TL;DR: Pilates exercises are suggested as an effective and safe method to improve physical capacity in AS patients and further research with more participants and longer follow-up periods could help assess the therapeutic value of this popular physical exercise method in AS.
Abstract: The objective of this study was to investigate the effects of Pilates on pain, functional status, and quality of life in patients with ankylosing spondylitis. The study was performed as a randomized, prospective, controlled, and single-blind trial. Fifty-five participants (30 men, 25 women) who were under a regular follow-up protocol in our Rheumatology Clinic with the diagnosis of AS according to the modified New York criteria were included in the study. The participants were randomly assigned into two groups: in group I, Pilates exercise program of 1 h was given by a certified trainer to 30 participants 3 times a week for 12 weeks, and in group II, designed as the control group, 25 participants continued previous standard treatment programs. In groups, pre-(week 0) and post treatment (week 12 and week 24) evaluation was performed by one of the authors who was blind to the group allocation. Primary outcome measure was functional capacity. Evaluation was done using the Bath Ankylosing Spondylitis Functional Index (BASFI). Exploratory outcome measures were Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Chest expansion, and ankylosing spondylitis quality of life (ASQOL) questionnaire. In group I, BASFI showed significant improvement at week 12 (P = 0.031) and week 24 (P = 0.007). In group II, this parameter was not found to have significantly changed at week 12 and week 24. Comparison of the groups showed significantly superior results for group I at week 24 (P = 0.023). We suggest Pilates exercises as an effective and safe method to improve physical capacity in AS patients. Our study is the first clinical study designed to investigate the role of Pilates method in AS treatment. We believe that further research with more participants and longer follow-up periods could help assess the therapeutic value of this popular physical exercise method in AS.

105 citations


Journal ArticleDOI
TL;DR: The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause.
Abstract: Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret is self-administered by daily subcutaneous injections in patients with active RA. The mechanism of action of anakinra is to competitively inhibit the local inflammatory effects of IL-1. Kineret is generally safe and well tolerated and the only major treatment-related side effects that appear are skin reactions at the injection site. Due to the relatively short half-life of anakinra, daily injection of the drug is required. This, in combination with the comparably high rates of injection-site reactions (ISRs) associated with the drug, can become a problem for the patient. The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause. The objective is also to present some clinical experiences of how the ISRs can be managed.

104 citations


Journal ArticleDOI
TL;DR: Infliximab, an anti-TNF-α drug, may be effective in the treatment of depression accompanying ankylosing spondylitis, and possible implications for thetreatment of major depressive disorder were discussed.
Abstract: The objective of this study was to assess the effect of infliximab on depression, anxiety and quality of life in patients with active ankylosing spondylitis (AS). In this 6-week longitudinal study, 16 patients with AS were assessed. Active disease as defined by BASDAI ≥4.0 was sought for inclusion. Infliximab was administered 5 mg/kg at 0, 2 weeks and 6 weeks. Collected data included age, sex and date of onset of rheumatologic disease. Activity of disease was measured using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Biological activity was evaluated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). ESR and CRP were assessed at baseline and day 42. The Hospital Anxiety and Depression scale (HADS), Beck Depression Inventory (BDI) and 36-item Short Form Health Survey (SF-36) were used to evaluate anxiety, depression and quality of life. BASDAI, SF-36, HADS and BDE were assessed prior to the initial infliximab dose and at 2nd, 14th and 42nd day. Seven (43.8%) AS patients had depression scores above the cut off value for both the HADS depression (HADS-D) and BDI and 4 (25 %) had high HADS anxiety scores at baseline. Significant time effect for BDI and HADS-D scores were observed. Although significantly lower BDI scores were found after first, second and third infusions of infliximab, compared to initial score, the significant decrease in HADS-D appeared after second and third infusions. A significant time effect for HADS-anxiety scores were found as well. All of the subscales of SF-36 improved significantly during the course, with an exception of role emotional, for which the difference approached to the significance. The change in BASDAI scores and CRP and ESR, in the treatment process, were not correlated with the change in depression and anxiety scores. Infliximab which is an anti-TNF-α drug, may be effective in the treatment of depression accompanying AS. Possible implications for the treatment of major depressive disorder were discussed, as well.

Journal ArticleDOI
TL;DR: MS was as effective as WA in reducing pain regarding all study variables; however, symptoms management during the follow-up period was more efficient in the WA group.
Abstract: The purpose of this study was to evaluate and compare the effectiveness of muscle-strengthening exercises (MS) and a walking program (WA) in reducing pain in patients with fibromyalgia. Ninety women, 30–55 years of age, diagnosed with fibromyalgia according to the American College of Rheumatology 1990 criteria, were randomized into 3 groups: WA Group, MS Group, and control group. Pain (visual analog scale) was evaluated as the primary outcome. Physical functioning (Fibromyalgia Impact Questionnaire, FIQ), health-related quality of life (Short-Form 36 Health Survey, SF-36), and use of medication were evaluated as secondary outcomes. Assessments were performed at baseline, 8, 16, and 28 weeks. Intention-to-treat and efficacy analyses were conducted. Sixty-eight patients completed the treatment protocol. All 3 groups showed improvement after the 16-week treatment compared to baseline. At the 28-week follow-up, pain reduction was similar for the WA and MS groups (P = 0.39), but different from the control group (P = 0.01). At the end of the treatment, 80% of subjects in the control group took pain medication, but only 46.7% in the WA and 41.4% in the MS groups. Mean FIQ total scores were lower for the WA and MS groups (P = 0.96) compared with the control group (P < 0.01). Patients in the WA and MS groups reported higher scores (better health status) than controls in almost all SF-36 subscales. MS was as effective as WA in reducing pain regarding all study variables; however, symptoms management during the follow-up period was more efficient in the WA group.

Journal ArticleDOI
TL;DR: There is now a large, convergent body of evidence that glucosamine sulfate, given at a daily oral dose of 1,500 mg, is able to significantly reduce the symptoms of osteoarthritis in the lower limbs.
Abstract: Over the last 20 years, several studies have investigated the ability of glucosamine sulfate to improve the symptoms (pain and function) and to delay the structural progression of osteoarthritis. There is now a large, convergent body of evidence that glucosamine sulfate, given at a daily oral dose of 1,500 mg, is able to significantly reduce the symptoms of osteoarthritis in the lower limbs. This dose of glucosamine sulfate has also been shown, in two independent studies, to prevent the joint space narrowing observed at the femorotibial compartment in patients with mild-to-moderate knee osteoarthritis. This effect also translated into a 50 % reduction in the incidence of osteoarthritis-related surgery of the lower limbs during a 5-year period following the withdrawal of the treatment. Some discrepancies have been described between the results of studies performed with a patent-protected formulation of glucosamine sulfate distributed as a drug and those having used glucosamine preparations purchased from global suppliers, packaged, and sold over-the-counter as nutritional supplements.

Journal ArticleDOI
TL;DR: Investigating the possible role of the OPG/RANKL system in RA-related bone loss found that in RA group, plasma rheumatoid factor concentration, swollen joint count, and the level of C-reactive protein in peripheral blood of RA were the risk factors for the occurrence of osteoporosis.
Abstract: Osteoporosis represents an important cause of morbidity in adult rheumatoid arthritis (RA) patients who exhibit increased fracture risk. It is thought that osteoclast and its dysfunction which mediated by many cytokines are the principal pathogenesis of this bone disease, although the mechanisms are still not fully understood. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been revealed in the pathogenesis of primary osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to investigate the possible role of the OPG/RANKL system in RA-related bone loss. A total of 64 Chinese patients with RA and 60 healthy control subjects were involved. Serum levels of OPG and RANKL were measured by ELISA. BMD of nondominant forearm, lumbar spine(L1–4) and proximal femur, including femoral neck, Wards triangle, greater trochanter were assessed using dual-energy X-ray absorptiometry. RA patients had a higher incidence of osteoporosis (23/64, 35.9%) than that in healthy controls (9/60, 15.0%) (P < 0.0001). They displayed lower BMD values than controls at positions of all detected region. Compared with healthy controls, RA group showed significantly higher serum levels of RANKL (48.4 ± 12.5 vs. 23.0 ± 11.2 pmol/l, P < 0.0001), lower serum levels of OPG (106.2 ± 40.6 vs. 231.6 ± 65.6 pg/ml, P < 0.0001), and OPG/RANKL ratio (2.4 ± 0.7 vs. 7.0 ± 1.1, P < 0.0001). Multiple linear regression analysis revealed that in RA group, plasma rheumatoid factor concentration (β = −0.187, P = 0.031), swollen joint count (β = 0.567, P = 0.029), BMD at forearm (β = 0.324, P = 0.002), femoral Wards triangle (β = 0.370, P < 0.0001), and lumbar spine (β = 0.313, P = 0.003) were the contributors for serum OPG (R 2 = 0.718, P < 0.0001). Age (β = 0.241, P = 0.042) and BMD at femoral Wards triangle (β = −0.441, P < 0.0001) and lumbar spine (β = −0.320, P = 0.013) were the determinants for serum RANKL (R 2 = 0.616, P < 0.0001), while swollen joint count (β = 1.029, P = 0.019) and BMD at femoral neck (β = 0.285, P = 0.042) for serum OPG/RANKL ratio (R 2 = 0.279, P < 0.011). Analysis of logistic regression showed age (P = 0.004, OR = 1.156, 95% CI: 1.047–1.276) and the level of C-reactive protein (P = 0.028, OR = 1.019, CI 95%: 1.002–1.036) in peripheral blood of RA were the risk factors for the occurrence of osteoporosis in RA, while OPG/RANKL ratio (P = 0.007, OR = 0.035, CI 95%: 0.003–0.400) was the unique protective factor. These data suggest that, in Chinese RA patients, an altered modulation of the OPG/RANKL system resulting in increased RANKL and decreased OPG in peripheral blood, could contribute to the bone loss characteristic and the generation of osteoporosis in these patients. Changes of ratio of OPG/RANKL might be a protective mechanism against the accelerated bone loss in RA.

Journal ArticleDOI
TL;DR: Serum DKK-1 level was lower in patients with ankylosing spondylitis than in healthy controls and did not change after 3 months of anti-TNF-α therapy in the AS patients despite the marked improvement in BASDAI scores, which suggest the low serum DKK -1 level is related to the pathogenesis of new bone formation in AS, which is resistant to TNF- α blocking therapy.
Abstract: (1) To compare the serum levels of Dickkopf-1 (DKK-1) and bone biomarkers in patients with ankylosing spondylitis (AS) and healthy controls. (2) To examine the effects of anti-tumor necrosis factor-α (TNF-α) therapy for 3 months on bone biomarkers in patients with AS. We measured the levels of DKK-1, osteocalcin, osteoprotegerin, and C-terminal telopeptide of type I collagen (CTX-1) in patients with AS and in healthy controls at baseline and 3 months after initiating anti-TNF-α therapy in AS patients. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were also measured before and after anti-TNF-α therapy in AS patients. Serum levels of DKK-1 were significantly lower in the AS patients than in the controls (P < 0.0001). Osteocalcin and osteoprotegerin levels were significantly higher in the AS patients than in the controls (P < 0.0001). Serum levels of DKK-1 were not changed after the 3-month anti-TNF-α therapy. Osteocalcin level increased (P < 0.0001), osteoprotegerin level and BASDAI scores decreased (P = 0.025 and P < 0.0001, respectively) significantly after the 3-months anti-TNF-α therapy. Serum DKK-1 level was lower in patients with AS than in healthy controls and did not change after 3 months of anti-TNF-α therapy in the AS patients despite the marked improvement in BASDAI scores. These findings suggest the low serum DKK-1 level is related to the pathogenesis of new bone formation in AS, which is resistant to TNF-α blocking therapy.

Journal ArticleDOI
TL;DR: Capillary microscopy is effective method for differentiation between primary and secondary RP and useful tool for the prediction of scleroderma spectrum disorders in RP patients.
Abstract: To assess the prognostic value of scleroderma pattern of nailfold capillary changes for the development of connective tissue diseases (CTD) in subjects with primary Raynaud’s phenomenon (RP). The study included 3,029 consecutive patients with primary RP who had been followed at 6-month intervals during the mean of 4.8 years. The pathological features of nailfold capillaroscopy were recorded in all patients who had neither clinical nor serological signs of a CTD. In patients who developed CTD, capillary changes obtained 6 months prior to diagnosis were analyzed. A possible relationship between capillary changes and the presence of associated CTD was assessed. At the end of follow-up, 1,660 (54,8%) patients have still the primary RP, 246 (8,1%) had suspected secondary RP, and 1,123 (37,1%) patients developed CTD (363 undifferentiated CTD, 263 systemic sclerosis, 143 systemic lupus erythematosus, 106 rheumatoid arthritis, 102 Sjogren’s syndrome, 61 overlap syndrome, 30 vasculitides, 24 mixed CTD, 19 polymyositis, 7 dermatomyositis, and 5 primary antiphospholipid syndrome). Scleroderma pattern were significantly associated with the development of systemic sclerosis [P = .00001, sensitivity 94%, specificity 92%, positive predictive value 52%, negative predictive value 99%, and odds ratio 163 (95% CI, 97,9–271,5)], as well as dermatomyositis (P = .0004), overlap syndrome with signs of systemic sclerosis (P = .0001), and mixed connective tissue disease (P = .007). Capillary microscopy is effective method for differentiation between primary and secondary RP and useful tool for the prediction of scleroderma spectrum disorders in RP patients.

Journal ArticleDOI
TL;DR: The prevalence’s of BD and FMF are considerably lower in Havsa as compared to other regions in Turkey, and these figures were adjusted for age-sex of the general Turkish population.
Abstract: To study the prevalence major rheumatic diseases in western Turkey. This survey was conducted in Havsa which have a total population of 18,771. Physicians and interns visited every household, interviewed face to face a questionnaire about the symptoms of rheumatic disorders. The individuals replied positively to any question were examined at the nearest health center. Those have no objective findings related to any rheumatic diseases were excluded. People could not be clinically diagnosed were asked to come to the hospital for further evaluation. A total 17,835 of 18,771 residents participated. We estimated the prevalence of Behcet's Disease (BD) as 0.019%; ankylosing spondylitis: 0.120%; rheumatoid arthritis: 0.321%; knee osteoarthritis (OA): 5.351%; hand OA: 1.110%; hand and knee OA: 1.958%; total OA: 8.420%; primary Raynaud's: 1.192%; psoriasis: 0.424 %; psoriatic arthritis: 0.050%; rheumatic fever: 0.318%; rheumatic heart disease: 0.200%; inflammatory bowel disease: 0.023%; lupus: 0.059%; gout: 0.018%; systemic sclerosis: 0.022%; juvenile rheumatoid arthritis: 0.032%; temporal arteritis: 0.020%, and familial Mediterranean fever (FMF) as 0.006%. Figures were adjusted for age-sex of the general Turkish population. The prevalence's of BD and FMF are considerably lower in Havsa as compared to other regions in Turkey.

Journal ArticleDOI
TL;DR: In Chinese PM/DM patients, serum anti-MDA5 antibody is mainly presented inDM patients and can be a useful marker for A/SIP in patients with DM and can predict unfavorable prognosis in DM patients with ILD.
Abstract: The aim of this study is to determine serum anti-melanoma differentiation-associated gene 5 prevalence and their clinical associations in Chinese patients with polymyositis and dermatomyositis (PM/DM). Serum anti-MDA5 antibody was detected by ELISA in 113 adult PM/DM patients and in various controls. Flow cytometry was applied to analyze the subgroups of lymphocytes in the peripheral blood of PM/DM patients. The serum anti-MDA5-positive rate in the DM patients (22.6%) was significantly higher compared with that in PM patients (0%, P < 0.005), patients with SLE (3.3%, P < 0.05), RA (3.3%, P < 0.05), pSS (0%, P < 0.05), pulmonary infection (0%, P < 0.05) and healthy controls (0%, P < 0.001). The percentage of decreased CD4+, CD8+ T cell counts, raised CD4+/CD8+ ratio in peripheral blood and the incidence of acute/subacute interstitial pneumonia (A/SIP) were significantly higher in anti-MDA5-positive DM group than negative group (all P < 0.05). Additionally, logistic multivariate analysis showed that anti-MDA5 is an independent risk factor for death of ILD in DM (OR = 8.46, 95% CI 1.77–40.36, P = 0.007). In conclusion, in Chinese PM/DM patients, serum anti-MDA5 antibody is mainly presented in DM patients and can be a useful marker for A/SIP in patients with DM. It can predict unfavorable prognosis in DM patients with ILD. Further studies are needed to identify how the abnormal T cells in peripheral blood participated in the generation of the anti-MDA5 antibody.

Journal ArticleDOI
TL;DR: The results suggest that some gait parameters recorded using the smartphone represent an acceptable assessment tool for gait in patients with rheumatoid arthritis.
Abstract: A disturbance in gait pattern is a serious problem in patients with rheumatoid arthritis (RA). The aim of the present study was to examine the utility of the smartphone gait analysis application in patients with RA. The smartphone gait analysis application was used to assess 39 patients with RA (age 65.9 ± 10.0 years, disease duration 11.9 ± 9.4 years) and age-matched control individuals (mean age, 69.1 ± 5.8 years). For all RA patients, the following data were obtained: disease activity score (DAS) 28, modified health assessment questionnaire (mHAQ), and assessment of walking ability. Patients walked 20 m at their preferred speed, and trunk acceleration was measured using a Smartphone. After signal processing, we calculated the following gait parameters for each measurement terminal: peak frequency (PF), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. The gait parameters of RA and control groups were compared to examine the comparability of the 2 groups. Criterion-related validity was determined by evaluating the correlation between gait parameters and clinical parameters using Spearman’s correlation coefficient. The RA group showed significantly lower scores for the walking speed, AC, and CV than the control group. There were no significant differences in PF. PF (gait cycle) was mildly associated with gait speed (P < 0.05). AC (gait balance) was moderately associated with the DAS, mHAQ, gait ability, and gait speed (P < 0.05). CV (gait variability) was moderately associated with the DAS, gait ability, and gait speed (P < 0.05). This is the first study to examine the use of a smartphone device for gait pattern measurement. The results suggest that some gait parameters recorded using the smartphone represent an acceptable assessment tool for gait in patients with RA.

Journal ArticleDOI
TL;DR: Great caution must continue to be exerted when initiating CS therapy, especially in high doses and in the early diffuse subset of SSc patients, although this may be due to confounding by disease severity and/or co-intervention.
Abstract: Scleroderma renal crisis (SRC) has been associated with the use of corticosteroids (CS) in retrospective studies. Using an evidence-based approach, we undertook a systematic review of the literature to identify prospective studies in which scleroderma patients were administered CS to ascertain the risk of SRC in those patients. A comprehensive search was conducted using Medline, EMBASE, the Cochrane Library, and Web of Science. All original prospective clinical studies were eligible if they enrolled SSc patients newly treated with CS. Selected studies were reviewed, and data extraction was systematically performed for the dose and duration of the CS intervention as well as the occurrence of SRC. Twenty-six studies with a total of 500 SSc patients commencing new CS therapy were included in the systematic review. Ten definite cases of SRC, equivalent to a rate of 2%, were identified. In the subset of early diffuse patients, the rate of SRC was 4%. All 10 definite cases of SRC occurred in patients who received medium- to high-dose CS therapy. Seven cases occurred in the setting of stem cell transplant. CS are associated with SRC, although this may be due to confounding by disease severity and/or co-intervention. Great caution must continue to be exerted when initiating such therapy, especially in high doses and in the early diffuse subset of SSc patients.

Journal ArticleDOI
TL;DR: Findings suggest that SF visfatin might involved in cartilage matrix degradation.
Abstract: The aim of this study is to investigate visfatin levels in both synovial fluid (SF) and plasma of patients with primary knee osteoarthritis (OA) and its relationship with biomarkers of cartilage degradation in SF. Thirty OA patients, 12 SF control, and 12 plasma control subjects were enrolled in this study. Visfatin levels in both SF and plasma were measured using enzyme-linked immunosorbent assay (ELISA). Degradation biomarkers of collagen II and aggrecan in SF were also measured. The radiographic grading of OA in the knee was performed by the Kellgren-Lawrence (KL) criteria. Compared to controls, OA patients had higher SF visfatin concentration (8.95 ± 2.5 vs. 4.48 ± 2.49 ng/ml, P < 0.001). SF visfatin levels in KL grade 4 were significantly elevated compared with those of KL grade 3 (10.57 ± 2.49 vs. 7.54 ± 1.5 ng/ml, P = 0.001). SF visfatin positively correlated with degradation biomarker of collagen II, CTX-II (r = 0.497, P = 0.005), and degradation biomarker of aggrecan, AGG1 (r = 0.451, P = 0.012) and AGG2 (r = 0.434, P = 0.017). These findings suggest that SF visfatin might involved in cartilage matrix degradation.

Journal ArticleDOI
Jing Wang1, Jiesheng Gao1, Jin-wei Chen1, Fen Li1, Jing Tian1 
TL;DR: Histological evaluation of cartilage tissue revealed a significantly reduced cartilage destruction; the evaluation also revealed the loss of matrix proteoglycan content in cartilage in resveratrol intervention groups compared to the model control.
Abstract: To observe the effect of resveratol on cartilage, chondrocyte apoptosis, and nitric oxide in experimental osteoarthritis (OA) of rabbit and to study the mechanism of resveratol in the treatment of osteoarthritis. Thirty New Zealand rabbits were randomly divided into 5 groups: group A (normal control group), group B (model control group), group C (resveratrol intervention high-dosage group), group D (resveratrol intervention middle dosage group), and group E (resveratrol intervention low-dosage group). The model of OA of the knee was established using Hulth technique in groups B, C, D, and E. After 4 weeks, group A and group B rabbits were administered daily a knees injection of dimethylsulfoxide (DMSO), whereas groups C, D, and E were administered daily a knees injection of resveratrol in DMSO in different dosages for 2 weeks. Daily dosage for rabbits of groups C, D, and E was fixed at 50, 20, and 10 μmol/kg, respectively. Then, the rabbits were killed, and the lateral cartilage sections of right femoral medial condyle were evaluated using a histological scoring system (HE the evaluation also revealed the loss of matrix proteoglycan content in cartilage in resveratrol intervention groups compared to the model control. Resveratrol reduced the apoptosis rate of chondrocyte and level of NO in the synovial fluid. In the above experiments of OA rabbits, the protective effects of resveratrol were enhanced with increased resveratrol dosage. Resveratrol controls the progression of experimental OA. One of the mechanism(s) responsible for this effect would include lowering of the apoptosis rate of chondrocyte and reducing the production of NO in experimental OA.

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TL;DR: Results indicate that local consumption of leptin in the joint cavity has a protective role against the destructive course of RA.
Abstract: Reports suggest leptin, which was initially described as a hormone that regulates food intake and energy balance, has an intimate relationship, and interacts with the immune system. Leptin consumption in the synovial cavity in patients with rheumatoid arthritis (RA) reported to have protective effect against erosion. To determine the difference in serum leptin and synovial/serum leptin ratio between RA and control and to assess whether these parameters correlate with systemic inflammation in RA. Also, the hypothesis that synovial/serum leptin ratio could be linked to joint erosion in RA was evaluated. The study subjects consisted of 40 consecutive patients with RA, 30 patients of them had knee effusion, and 30 controls. Ten of these controls had acute knee injury and their synovial fluid was obtained for comparison of synovial/serum leptin ratio with patients with RA. The mean serum leptin in patients with RA was significantly higher than controls. Also, the synovial leptin and synovial/serum leptin ratio in the RA patients with effusion was significantly higher than in the 10 control subjects with traumatic effusion. Serum leptin in the 30 RA patients with effusion was higher than the matched synovial leptin. In RA patients with effusion, synovial/serum leptin ratio was also significantly higher in RA patients with erosion than RA patients without erosion. Serum leptin level and synovial/serum leptin ratio are significantly correlated with the RA duration, DAS28, ESR, CRP, TNF-α, and IL-6. Finally, in regression analysis, only the synovial/serum leptin ratio was positively associated with erosion in patients with RA. In RA, there is a significant increase in circulating leptin levels and synovial/serum leptin ratio compared to non-RA controls. Serum leptin and synovial/serum leptin ratio are significantly in erosive RA than non-erosive RA. Both parameters are correlated with disease duration and parameters of RA activity. In regression analysis, only the synovial/serum leptin ratio was positively associated with erosion in patients with RA. These results indicate that local consumption of leptin in the joint cavity has a protective role against the destructive course of RA.

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TL;DR: The efficacy of anakinra is reported in a 52-year-old Turkish patient with FMF, secondary amyloidosis and renal transplant, who was resistant to colchicine treatment.
Abstract: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limited recurrent attacks of fever and serositis. The serious complication of FMF is AA-type amyloidosis, which can result in end-stage renal disease. Although colchicine is effective in the majority of patients, there is no established treatment for those who are resistant or intolerant to colchicine. We herein report the efficacy of anakinra in a 52-year-old Turkish patient with FMF, secondary amyloidosis and renal transplant, who was resistant to colchicine treatment.

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TL;DR: The Turkish version of the fatigue severity scale (FSS) has been proved to be valid and reliable to detect severity of fatigue in fibromyalgia patients and recommended for use in clinical practice.
Abstract: The aim of the study was to investigate the validity and reliability of the Turkish version of the fatigue severity scale (FSS) in fibromyalgia (FM) patients Sixty-one FM patients and 54 healthy controls were evaluated using the Turkish version of the FSS Reliability was investigated using test–retest reliability and internal consistency Concurrent validity was evaluated between the FSS score and the VAS fatigue Convergent validity was assessed by comparing the FSS score with the scores of VAS pain, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Fibromyalgia Impact Questionnaire (FIQ) Spearman’s rank correlation coefficient was used to evaluate validity Test–retest reliability and internal consistency of the FSS were excellent in FM patients (ICC: 094, Cronbach’s alpha coefficient: 085) and in the healthy controls (ICC: 090, Cronbach’s alpha coefficient: 091) For the concurrent validity, the correlation between the FSS and VAS fatigue was very good in FM group (r: 063, P: 0000) and in the healthy controls (r: 094, P: 0000) For the convergent validity, correlations between the FSS and BDI, BAI, FIQ, pain intensity were moderate to good in both groups (P: 0000) The Turkish version of the FSS has been proved to be valid and reliable to detect severity of fatigue in FM patients We recommend the use of it in clinical practice

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TL;DR: A 68-year-old man, who was a patient with established rheumatoid arthritis with RA-associated interstitial lung disease (RA-ILD) and pulmonary emphysema, began taking tocilizumab and developed dyspnea parallel to improvement of RA and died despite receiving steroid pulse therapy and antibiotics on a respirator.
Abstract: A 68-year-old man, who was a patient with established rheumatoid arthritis (RA) with RA-associated interstitial lung disease (RA-ILD) and pulmonary emphysema, began taking tocilizumab. Subsequently, he developed dyspnea parallel to improvement of RA. At 10 months after the administration of tocilizumab, he was urgently admitted because of exacerbation of ILD. He died despite receiving steroid pulse therapy and antibiotic therapy on a respirator. This is the first case report to describe the exacerbation of ILD during treatment with tocilizumab in the postmarketing surveillance (PMS) period.

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TL;DR: The results suggest that better knowledge of the main biological processes involved at a given pattern in TCM might help to choose the most appropriate treatment.
Abstract: The research is aimed to explore the distinct molecular signatures in discriminating the rheumatoid arthritis patients with traditional Chinese medicine (TCM) cold pattern and heat pattern. Twenty patients with typical TCM cold pattern and heat pattern were included. Microarray technology was used to reveal gene expression profiles in CD4+ T cells. The signal intensity of each expressed gene was globally normalized using the R statistics program. The ratio of cold pattern to heat pattern in patients with RA at more or less than 1:2 was taken as the differential gene expression criteria. Protein–protein interaction information for these genes from databases was searched, and the highly connected regions were detected by IPCA algorithm. The significant pathways were extracted from these subnetworks by Biological Network Gene Ontology tool. Twenty-nine genes differentially regulated between cold pattern and heat pattern were found. Among them, 7 genes were expressed significantly more in cold pattern. Biological network of protein–protein interaction information for these significant genes were searched and four highly connected regions were detected by IPCA algorithm to infer significant complexes or pathways in the biological network. Particularly, the cold pattern was related to Toll-like receptor signaling pathway. The following related pathways in heat pattern were included: Calcium signaling pathway; cell adhesion molecules; PPAR signaling pathway; fatty acid metabolism. These results suggest that better knowledge of the main biological processes involved at a given pattern in TCM might help to choose the most appropriate treatment.

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TL;DR: The highest dose corticosteroid administered within 4 months and total cumulative prednisolone dose were significantly higher in the SLE patients with AVN, and the use of cytotoxic agent significantly higher proportion of patients withAVN.
Abstract: The objective was to investigate the predictive factors for avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE). The records of 868 patients with SLE from four centers were reviewed retrospectively. Forty-nine patients with AVN were identified. A total of 154 patients with SLE who did not have clinically apparent AVN during the follow-up were evaluated as a control group. The demographic, clinical, laboratory and management characteristics of these two groups of patients were recorded according to predefined protocol and compared. The prevalence of AVN was detected 6% in our SLE population. The highest dose corticosteroid administered within 4 months and total cumulative prednisolone dose were significantly higher in the SLE patients with AVN. The use of cytotoxic agent significantly higher proportion of patients with AVN. AVN tends to develop more frequently in male gender and younger patients. Oral ulcer, pleuritis, Raynaud’s phenomenon, cutaneous vasculitis, lymphadenopathy, autoimmune thyroiditis, peripheral neuropathy and Sjogren’s syndrome were higher incidence in SLE patients with AVN. The bilateral femoral heads were the commonest site of involvement of AVN in our patients with SLE.

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TL;DR: Comparing the microRNA profiles of patients with systemic scleroderma and healthy control individuals suggests that miRNAs may be potential diagnosis biomarkers and are likely to be involved in the pathogenesis of SSc.
Abstract: MicroRNAs are short, 18- to 25-nt sequences of noncoding, single-stranded RNA that function as regulatory molecules and participate in a series of vital processes including early development, cell proliferation, cell differentiation, apoptosis, substance metabolism and the pathogenesis of human diseases. This study compared the microRNA profiles of patients with systemic scleroderma (SSc) and healthy control individuals to investigate the pathogenesis of SSc. Skin tissue was isolated from three patients with SSc and three healthy controls. miRNA microarray chip analysis identified 24 miRNAs that were differentially expressed in patients with SSc and 6 microRNAs that may be correlated with the pathogenesis of SSc. The results of the microarray analysis were confirmed using real-time PCR. This work suggests that miRNAs may be potential diagnosis biomarkers and are likely to be involved in the pathogenesis of SSc.

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TL;DR: The results of this study might indicate that OGD should be performed early in patients diagnosed with SSc, even if they do not report typical symptoms, and an early diagnose of GI involvement might be followed by an effective therapy and therefore subsequently may improve the prognosis.
Abstract: Investigation into the upper GI-tract of patients suffering from systemic sclerosis [SSc] and mixed connective tissue disease [MCTD] without symptoms of GI-tract involvement early in the course of the disease to diagnose inflammatory and motility disorders. We retrospectively analysed patients with SSc and MCTD who underwent oesophago-gastro-duodenoscopy [OGD] within a year of the first diagnosis. Patients with a Rodnan skin score above 5, proton pump inhibitors and treatment regimes potentially harmful to the mucosa of the upper GI-tract were excluded. Mucosal damage of the oesophagus was classified according to the Los Angeles Classification. Oesophageal dysmotility was assessed during OGD and confirmed by video cineradiography. A total of thirteen patients with SSc and six with MCTD fulfilled the inclusion criteria. OGD revealed reflux-oesophagitis in 77%, dysmotility of the distal oesophagus in 85%, gastritis in 92% [31% erosive gastritis] and Helicobacter pylori positivity in 38% of our patients suffering from SSc. Patients with MCTD showed features of reflux-oesophagitis, dysmotility of the distal oesophagus, gastritis and dysmotility of the stomach in 0.6%. In all thirteen patients with SSc, significant pathology of the upper GI-tract was found. The results of this study might indicate that OGD should be performed early in patients diagnosed with SSc, even if they do not report typical symptoms. An early diagnose of GI involvement might be followed by an effective therapy and therefore subsequently may improve the prognosis.